Extracapsular lens extraction has become the method of choice for removing cataracts. The major medical advantages of this technique over intracapsular extraction are lower incidence of aphakic cystoid macular edema and retinal detachment. Extracapsular extraction is also required for implantation of posterior chamber type intraocular lenses which are now considered to be the lenses of choice in most cases.
A disadvantage of extracapsular cataract extraction is the high incidence of posterior lens capsule opacification, often called after-cataract, which can occur in up to 50% of cases within three years after surgery. After-cataract can be treated by additional surgical procedures (e.g., posterior capsulotomy, repolishing of the posterior lens capsule, or disruption of capsule by infrared energy from a neodymium YAG laser) to obtain good vision. There are complications associated with all types of capsulotomy. These include cystoid macular edema, retinal detachment, and transient or permanent glaucoma.
After-cataract is caused by proliferation of equatorial and anterior capsule lens epithelial cells which remain after extracapsular lens extraction. These cells proliferate to cause Sommerling rings, and along with fibroblasts which also deposit and occur on the posterior capsule, cause opacification of the posterior capsule, which interferes with vision. Prevention of after-cataract would be preferable to treatment, and could be achieved by physically or chemically destroying the lens cells at the time of the original cataract extraction.
In animal experiments, cytotoxic drugs administered during surgery or implantation have been investigated as a means of inhibiting the growth of lens epithelial cells. An example of such a drug is methotrexate (MTX), as described in U.S. Pat. No. 4,515,794. MTX kills dividing cells preferentially, though not exclusively, and is used in cancer chemotherapy.
As described in the above patent, MTX has been used as a mitotic inhibitor by instilling a solution containing a specific concentration of methotrexate into the anterior chamber of the eye after lens removal. Furthermore, the solution containing MTX is osmotically balanced to provide minimal effective dosage when instilled into the anterior chamber of the eye, thereby inhibiting subcapsular epithelial growth.
However, because MTX is not specific as to the type of cell that it kills, serious side effects can occur. Moreover, epitheliel cells must divide for MTX to exert its cytotoxic effect. The drug should therefore remain in the eye at least through the generation time of the lens epithelial cells. While these cells normally divide very slowly and only at the equator, division is stimulated by injury, such as would occur during surgery, occurring within 48 hours. Mitotic inhibitors comprised simply of solutions of methotrexate or other cytotoxins which are instilled in the aqueous fluid of the eye would be continually diluted by inflow of aqueous fluid which is renewed with a half time of about three hours. This dilution in turn decreases the ability of the drug to inhibit growth of the epithelial cells which remain after lens extraction.